Aptamers or oligonucleotide ligands are short nucleic acids that are capable of binding to target molecules such as proteins with high specificity and affinity. These oligonucleotides represent a new class of ligands that may be utilized in a variety of applications such as pharmaceuticals, diagnosis and research. However, the current technology for selection of such ligands. namely SELEX, is inefficient and time consuming. The first objective of this proposal is to develop a novel approach that will drastically increase the efficiency of selection process. This will be achieved mainly by a selection procedure that is based on affinity of the ligands, that significantly increases the signal-noise ratio, and that can be accomplished in a single step. Direct sequencing of individually collected beads will eliminate cloning steps, further improving the efficiency. The ultimate objective of this proposal is to develop oligonucleotide ligand matrix for affinity purification of target molecules. The oligonucleotide ligand affinity matrix offers distinct advantages such as low cost, safe, stable. highly specific and efficient, over competing technologies. In combination, this proposal will provide powerful tools to isolate oligonucleotide ligands and to reduce the cost of biomedical products dramatically at research and industrial scale. PROPOSED COMMERCIAL APPLICATIONS: This proposal intends to provide an efficient and robust approach to isolate specific oligonucleotide ligands that may be utilized in pharmaceuticals, diagnosis, research such as functional genomics. and industry. Ultimately,. this proposal aims to use oligonucleotide ligands matrix in affinity purification process to produce recombinant biopharmaceutical agents, such as enzymes, antibodies, hormones, receptors, antigens and small molecules.